Transcranial alternating current dynamic frequency stimulation (tacs)  system and method for alzheimers and dementia

ABSTRACT

Transcranial electrostimulation systems and methods are contemplated in which a high current level, charge balanced alternating current electrical signal is generated for delivery to the occipital region of a patient&#39;s brain. By stimulating the brain with a charged balanced stimulation current with a stimulation current envelope defining one or more series of pulses at particular frequencies and durations designed to evoke metabolic response in the neurons, significant improvements in efficacy and reductions in patient discomfort may be achieved relative to earlier methods of transcranial electrical stimulation, especially those in which result in a resultant rectified direct current component being administered to the patient. Further advantages, especially in promoting neural entrainment, may be realized as well via utilizing multiple series of pulses at different frequencies, and via the dynamic adjustment of the stimulation waveform via incorporation of feedback signals in order to maintain charge balance in real-time.

CROSS-REFERENCE TO RELATED APPLICATIONS

This application relates to and claims the benefit of U.S. ProvisionalApplication No. 63/054,964 filed Jul. 22, 2020 and entitled“TRANSCRANIAL ALTERNATING CURRENT DYNAMIC FREQUENCY STIMULATION (TACS)SYSTEM AND METHOD FOR ALZHEIMERS AND DEMENTIA” the entire disclosure ofwhich is hereby wholly incorporated by reference, and this applicationrelates to and claims the benefit of U.S. Provisional Application No.63/061,225, filed Aug. 5, 2020 and entitled “TRANSCRANIAL ALTERNATINGCURRENT DYNAMIC FREQUENCY STIMULATION (TACS) SYSTEM AND METHOD FORALZHEIMERS AND DEMENTIA” the entire disclosure of which is hereby whollyincorporated by reference.

STATEMENT RE: FEDERALLY SPONSORED RESEARCH/DEVELOPMENT

Not Applicable

BACKGROUND 1. Technical Field

The present disclosure relates generally to the field of transcranialelectrostimulation. More particularly, the present disclosure relates toimproved systems and methods for transcranial electrostimulation fortreating Alzheimer's Dementia and other dementia diseases.

2. Related Art

Electrostimulation devices for applying current to a patient throughelectrodes located on the head have been developed and used for avariety of purposes in the past, such as for producing analgesiceffects, inducing sleep, and reducing or controlling migraine headaches.Generally, such treatments are referred to as transcranialelectrostimulation (TCES) or cranial electrostimulation (CES).Conventional TCES devices, although employed for a number of differentpurposes, may have severe drawbacks. For example, many conventional TCESdevices utilize a direct current (DC) component in order to break downor lower the resistance of the skin and to allow the treatment current(which may a combination of direct and alternating current) to penetrateto the nervous system.

The presence of a DC component of a treatment current produced by a TCESdevice generally results in an unpleasant experience for a patientundergoing TCES therapy. In early TCES designs, the presence of the DCcurrent invariably would result in intense pain or burns to the skin ofthe wearer, requiring the placement of thick conductive padding betweenthe electrodes and the skin of the wearer in order to render thetreatment bearable. Even in more recently developed TCES therapies inwhich the levels of DC current are limited, these limited amounts of DCcurrent still often result in substantial user discomfort. Additionally,even when only an alternating current is applied to the skin, the layersof the skin generally result in a non-linear, complex impedance thatinvariably rectifies the AC signal and generates a DC component. This DCcomponent depolarizes nociceptors in the skin, causing discomfort in thepatient. If the DC-stimulated nociceptors are efferent to a trigeminalnerve branch in the head, the discomfort may be protected into theforehead region.

This patient discomfort resulting from DC rectification presents anupper limit on the amount of power that can be delivered even in anAC-only TCES therapy. Because of this upper limit on power, suchconventional therapies are limited in their efficacy. This is especiallypronounced when it may be desired to utilized TCES therapy to treatDementia diseases such as Alzheimer's Dementia, where the amount ofpower delivered may be insufficient to penetrate into the deepstructures in the brain associated with early Dementia and loss ofmemory and cognition.

Therefore, novel systems and methods for transcranial electrostimulationare desirable.

BRIEF SUMMARY

To solve these and other problems, novel systems and methods fortreating a patient for Alzheimer's Dementia (AD) are contemplated inwhich a transcranial electrostimulation system produces a high currentlevel, dual symmetric charge balanced alternating current electricalsignal for delivery to the occipital region of a patient's brain. Bystimulating the brain with a charged balanced AC stimulation currenthaving a stimulation current envelope defining a series of pulses havinga particular frequency, with the stimulation current being delivered fora particular duration, together designed to evoke particular metabolicresponses in the neurons, significant improvements in efficacy andreductions in patient discomfort may be achieved relative to earliermethods of transcranial electrical stimulation, especially those inwhich a direct current or a resultant rectified direct current componentis administered to the patient. Further advantages, especially inpromoting neural entrainment, may be realized as well via delivery ofthe charged-balanced stimulation current such that its envelope definesmultiple series of pulses at different frequencies, and via the dynamicalteration of the stimulation current via incorporation of feedbacksignals in order to maintain charge balance in real-time, in order tomaintain charge balance.

Transcranial electrostimulation systems for treating a patient forAlzheimer's Dementia are contemplated which may comprise a carrierwaveform generator, a stimulation current generator, and a patientcable. A stimulation current may be generated from an carrier waveformoutput from the carrier waveform generator, with the carrier waveformbeing an alternating current having a duty cycle ratio and a currentamplitude ratio, the duty cycle ratio and the current amplitude ratiobeing selected such that each respective integration of the currentamplitude between successive time instances at which the carrierwaveform alternates polarity is substantially equivalent. Thestimulation current may be subsequently conveyed to the patient via thepatient cable.

The contemplated transcranial electrostimulation systems for treating apatient for Alzheimer's Dementia may further be configured to amplitudemodulate the carrier waveform prior during the process of generating thestimulation current, such that the extremes of the stimulation currentdefine a stimulation current envelope. The stimulation current envelopemay further be amplitude modulated such that the stimulation currentenvelope defines a first series of pulses occurring at a firstfrequency. The frequency of the first series of pulses may be about 40Hz.

The contemplated transcranial electrostimulation systems for treating apatient for Alzheimer's Dementia may further be configured to generate astimulation current wherein the stimulation current envelope furtherdefines a second series of pulses occurring at a second frequency.According to certain exemplary embodiments, the second series of pulsemay occur at a frequency selected from: about 4 Hz, about 40 Hz, about77.5 Hz.

The contemplated transcranial electrostimulation systems for treating apatient for Alzheimer's Dementia may further be configured such that thestimulation current is conveyed to the patient for a treatment duration,with the stimulation current defining a stimulation current envelope,the stimulation current envelope defining a first series of pulses thatoccur at a frequency of about 40 Hz for the entire treatment duration,and defining a second series of pulses that occur at a frequency ofabout 4 Hz for a first portion of the treatment duration, a frequency ofabout 40 Hz for a second portion of the treatment duration, and afrequency of about 77.5 Hz for a third portion of the treatmentduration. The treatment duration may be, for example, about an hour,with each of the first portion of the treatment duration, the secondportion of the treatment duration, and the third portion of thetreatment duration being about 20 minutes.

According to various further refinements of the contemplatedtranscranial electrostimulation systems, the stimulation current may beconfigured such that it defines a stimulation current envelope whichitself defines a plurality of series of pulses, each respective one ofthe plurality of series of pulses occurring at a respective frequency.In even further refinements of the above concept, each of the pluralityof series of pulses defined by the stimulation current envelopes has afrequency selected from one or more of: about 4 Hz, about 40 Hz, about77.5 Hz.

The transcranial electro stimulation systems for treating a patient forAlzheimer's Dementia may further be configured such that the carrierwaveform may have a frequency of about 100 KHz, such that the thecarrier waveform is a rectangular wave, or both.

According to various further refinements of the contemplatedtranscranial electrostimulation systems, the system(s) may furthercomprise one or more reference electrodes, the stimulation current beingmeasured at the patient by the one or more reference electrodes and anelectrode contact impedance being determined therefrom, and a controllerin communication with the one or more reference electrodes, thecontroller adjusting, based upon the determined electrode contactimpedance, one or more parameters of: the carrier waveform output fromthe waveform generator, the stimulation current output from thestimulation current generator, or combinations thereof.

Methods for treating a patient for Alzheimer's Dementia are alsocontemplated, with such methods comprising the steps of: (a) generatinga carrier waveform, the carrier waveform being an alternating currenthaving a duty cycle ratio and a current amplitude ratio, the first dutycycle ratio and the first current amplitude ratio being selected suchthat each respective integration of the current amplitude betweensuccessive time instances at which the first waveform alternatespolarity is substantially equivalent; and generating a stimulationcurrent from the carrier waveform via amplitude modulation the carrierwaveform, the extremes of the stimulation current defining a stimulationcurrent envelope, the stimulation current envelope defining a firstseries of pulses occurring at a first frequency; and (b) applying thestimulation current to the occipital region of the brain of the patient.According the particular refinements of such methods, the first seriesof pulses may occur at a frequency of about 40 Hz.

The step of generating a stimulation current may, in additionalembodiments, occur via amplitude modulating the carrier waveform suchthat the stimulation current envelope current further defines a secondseries of pulses occurring at a second frequency. The frequency of thesecond series of pulses may be selected from, for example, about 4 Hz,about 40 Hz, or about 77.5 Hz.

The above described methods may also comprise applying the stimulationcurrent to the occipital region of the brain of a to a patient for atreatment duration, wherein the first series of pulses occur at afrequency of about 40 Hz for the entire treatment duration, and whereinthe second series of pulses occur at a frequency of about 4 Hz for afirst portion of the treatment duration, a frequency of about 40 Hz fora second portion of the treatment duration, and a frequency of about77.5 Hz for a third portion of the treatment duration. The treatmentduration may be, for example, an hour, with each of the first portion ofthe treatment duration, the second portion of the treatment duration,and their third portion of the treatment duration being about 20minutes.

According to further refinements of the above described methods, thestep of generating the stimulation current may be performed viaamplitude modulating the carrier waveform such that the stimulationcurrent envelope defines a plurality of series of pulses, eachrespective one of the plurality of series of pulses occurring at arespective frequency. Such frequencies may be selected from one or moreof: about 4 Hz, about 40 Hz, about 77.5 Hz. Further, it is contemplatedthat the carrier waveform may have a frequency of about 100 KHz, may bea rectangular wave, or both.

In further refinements of the above described methods, additional stepsmay be included such as: measuring the stimulation current at thepatient, determining of an electrode contact impedance therefrom, andbased upon the determined electrode contact impedance, adjusting one ormore of: the waveform output from the waveform generator, thestimulation current output from the stimulation current generator, orcombinations thereof.

A method of generating a stimulation current is also contemplated, withthe method comprising generating a carrier waveform, the carrierwaveform being a rectangular alternating current having a duty cycleratio and a current amplitude ratio, the duty cycle ratio and thecurrent amplitude ratio being selected such that each respectiveintegration of the current amplitude between successive time instancesat which the waveform alternates polarity is substantially equivalent,and amplitude modulating the carrier waveform to derive a stimulationcurrent, the extreme of the stimulation current defining a stimulationcurrent envelope, the stimulation current envelope defining a firstseries of pulses occurring at a first frequency.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1 is an illustration showing an embodiment of a high frequency (100KHz) rectangular alternating current carrier waveform that ischarge-balanced, in that the area under the curves (AUC) for eachrespective integration of current amplitude between successive timeinstances at which the carrier alternates polarity is equal, with suchcharge balance resulting from the choice of a particular duty cycleratio (T2:T1) and a particular current amplitude ratio (Ma(1):Ma(2)) forthe carrier waveform;

FIG. 2 is an illustration showing one embodiment of stimulation currentcomprising the result of amplitude modulating the carrier waveform ofFIG. 1 such that the extremes of the stimulation current define astimulation current envelope, with the stimulation current envelopedefining a first series of pulses occurring at a frequency F1 and havinga pulse width PW1.

FIG. 3 is an illustration showing another embodiment of a stimulationcurrent comprising the result of amplitude modulating the carrierwaveform of FIG. 1 such that the extremes of the stimulation currentdefine a stimulation current envelope, with the stimulation currentenvelope defining a first series of pulses occurring at a frequency F1and having a pulse width PW1, and defining a second series of pulsesoccurring at frequency F2 and having a pulse width PW2;

FIG. 4 is an illustration showing an example of a resultant rectifiedcharge that is entrained at the neurons within the occipital region of apatient's brain, overlaid atop the example of the stimulation currentshown in FIG. 2, the resultant rectified charge occurring as aconsequence of transcranial application of the illustrated stimulationcurrent to occipital region of a patient's brain.

FIG. 5 is a flowchart showing certain steps of an embodiment of a methodfor treating a patient for Alzheimer's Dementia;

FIG. 6 is a block diagram showing certain hardware components of anembodiment of a transcranial electrostimulation system for treating apatient for Alzheimer's Dementia;

FIG. 7 is a block diagram showing, in greater detail, certain hardwareand/or software components of a stimulation circuitry PCB included inone embodiment of a transcranial electrostimulation system for treatinga patient for Alzheimer's Dementia;

FIG. 8 is a block diagram showing certain hardware and/or softwarecomponents of a front panel of an embodiment of a transcranialelectrostimulation system for treating a patient for Alzheimer'sDementia; and

FIG. 9 is an exemplary image of a front panel user interface of anembodiment of a transcranial electrostimulation system for treating apatient for Alzheimer's Dementia.

DETAILED DESCRIPTION

According to various aspects of the present disclosure, new systems andmethods for transcranial electrostimulation (TCES) are contemplated inwhich a “symmetric” or charge balanced AC signal is delivered to thepatient in a manner that permits higher levels of overall power to betransmitted more deeply into the brain without the limitations of thepatent discomfort threshold, permitting evocation of nerves in the deepbrain structures and enhancing treatment outcome. This increase in powermay enhance treatment efficacy and response without any adverse clinicalsequelae. By amplitude modulating the carrier waveform to incorporatinga blend of multiple frequency patterns of the series of pulses definedby the stimulation current envelope into the treatment, such as a firstfrequency pattern at 40 Hz for an entire one hour treatment duration,and a second frequency pattern in a sequence of 4 Hz, 40 Hz, and 77.5 Hzfor 20 minutes each, the blended frequency pattern of the stimulationcurrent envelope may result in metabolic cleansing and regeneration indamaged neurons, which in particular may be seen to reduce and possiblyreverse the symptoms associated with dementia diseases such asAlzheimer's Dementia (AD).

Turning now to FIG. 1, an exemplary embodiment of a rectangularalternating current (AC) carrier waveform is illustrated. As may beseen, the exemplary rectangular AC carrier waveform has, between eachsuccessive alternation of polarity, an area under the curve (AUC), i.e.the integration of the current amplitude between successive timeinstances at which the waveform alternates polarity. For the waveform tobe “symmetric” or “change balanced,” each successive pair of AUC betweenpolarity shifts in the AC waveform must be equal. Via the originalrectangular AC carrier waveform being charged balanced in this fashion,it may be seen that the ultimate stimulation current derived fromamplitude modulating this waveform will not result in undesiredrectification when applied to the patient's skin and thus will notresult in the production of a DC component that will cause discomfort orpain in the patient.

The carrier waveform itself may be any type of alternating currentwaveform. In the exemplary embodiment of FIG. 1, it may be seen that thewaveform is generally in the form of a rectangular wave. However, it maybe seen that other waveform types may be used as carrier waveforms, suchas sinusoidal or triangular waves. It may also be seen that this chargebalancing, wherein the AUC of each successive pair of region betweenalternation in polarity are substantially equivalent, may be achieved ina variety of ways, such that each respective pair of waveforms is notnecessarily required to have the same geometry as those preceding it. Asshown in the image, the “on” positive amperage portions of theillustrated carrier waveform have a greater magnitude than the “off”negative amplitude portions, but are of a shorter duration (T2), withthe duration of the “off” negative amperage portions of the carrierwaveform being longer (T1-T2) and with a lesser magnitude. This ratio ofthe time when the carrier waveform “on” versus “off” is referred to asthe duty cycle ratio, which is calculated here, when a rectangular ACwaveform is used as the carrier wave, as (T2)/(T1). It may be seen thatby controlling the relative magnitudes of the amperages, durations, andpossibly even the shape itself of the carrier waveform or portionsthereof (especially in non-square waveforms), a carrier waveform may beachieved that is charge balanced. Thus it may be seen that in the caseof a dynamic signal, when the duty cycle ratio (T2/T1) of the waveformis changed, so must the current amplitude ratio (mA(1)/mA(2)) also bechanged to compensate and maintain the charge balanced nature of thewaveform in order to prevent the ultimate stimulation current producedfrom producing a rectified DC component at the patients' skin whenapplied to the patient. For example, with a rectangular waveform, thefollowing Table 1 shows various duty cycles and corresponding carrieramplitude ratio pairings that will result in a charge balanced waveform:

TABLE 1 Charged Balanced Duty Cycle Ratio and Current Amplitude RatioPairings Duty Cycle Ratio Current Amplitude Ratio 1:3 2:1 1:4 3:1 1:54:1

In the exemplary embodiment, the carrier waveform is a high-frequencyrectangular alternating current, which has a frequency of about 100 KHz.It has generally been found that use high frequency carrier waveform ismost beneficial for permitting deep penetration of the stimulationcurrent into targeted regions of the patient's brain. However, in otherembodiments, it is contemplated that higher or lower frequencies than100 KHz may be utilized, without departing from the scope and spirt ofthe present disclosure. Likewise, it may also be seen that variation inthe frequency of the carrier waveform over time or in response tostimuli or other inputs may be utilized in order to enhance thefunctionality of the transcranial electrostimulation device.

Turning now to FIG. 2, an exemplary embodiment of a stimulation currentthat has been produced via amplitude modulation of the high frequencycarrier waveform of FIG. 1 is illustrated. As may be seen, the extremesof the amplitude modulated high frequency carrier waveform define astimulation current envelope, which results as a consequence of theparticular parameters of the amplitude modulation. The stimulationcurrent envelope may itself be seen to define a first series of pulsesoccurring at a first frequency F1 and having a pulse width PW2. Whenapplied to the occipital region of the patient's brain, the stimulationcurrent may induce neural entrainment, causing neurons within thepatient's brain to be stimulated an via polarization of the electricalcharge on the outside of the membrane in accordance with the frequencyof the first series of pulses. As long as the magnitude and pulse widthof the pulses defined by the stimulation current envelope are sufficientto promote neural stimulation and trigger an action potential, and aslong as the frequency of the series of pulses are not too high so as topermit the neuron to complete its refractory period prior to excitationvia the subsequent pulse, neural entrainment may occur at the neuronsthat are affected by the stimulation current.

Turning now to FIG. 3, another exemplary embodiment of a stimulationcurrent is illustrated in which the original carrier waveform shown inFIG. 1 has been amplitude modulated such that a first and a secondseries of pulses are defined by the stimulation current envelope, thefirst series of pulses having a frequency F1 and a pulse width PW1, andthe second series of pulses having a frequency F2 and a pulse width PW2.It may be seen that in this embodiment, the second series of pulsesoccur at a higher frequency (F2), have a shorter pulse width, and are ofa lesser magnitude than the pulses within the first series of pulses.However, it may be seen that in other embodiments of stimulationcurrents, the pulses of one series of pulses may have higher or lowerfrequencies, shorter or longer pulse widths, and greater or lessermagnitudes than the pulses of another series of pulses, withoutdeparting from the scope and spirit of the presently contemplatingdisclosure. In this manner, it may be seen that such a stimulationcurrent defining an envelope with multiple series pulses may be created.As a result, by optimizing the parameters of the pulses of each seriesof pulses, neural entrainment of certain neurons within the patient'sbrain may be facilitated at Frequencies F1 and/or F1 when thestimulation current is delivered to the patient, with the stimulatingcurrent still being charge balanced and not resulting in substantialpatient discomfort. By, for example, configuring the stimulation currentto have different pulse widths or amplitudes for certain of the seriesof pulses, it may be seen that certain types or regions of neurons maybe targeted by some of the series of pulses for neural entrainment,while other types or regions of neurons may be targeted by others of theseries of pulses for neural entrainment.

It may also be seen that other types of schemes for creating a combinedstimulation current envelope having other features may be utilized, suchas those in which the stimulation current is generated in which thestimulation current envelope defines three or more series of pulses,each series of pulses which may have different parameters in order tofacilitate neural entrainment of different types of neurons, or in whichthe frequencies of the series of pulses defined by the stimulationcurrent envelope are adjustable or configured to adjust according to thereceipt of or other feedback, stimuli, or other inputs at thetranscranial electrostimulation device.

According to certain exemplary embodiments, in particular it has beendiscovered that by administering a charge balanced stimulation currentwhich contains a blend of different frequency patterns, neuronalresponses within a patient's brain may be evoked which may tend toresult in metabolic cleansing and regeneration in damaged neurons.Notably, it is contemplated that administration of a charged balancedstimulation current having a stimulation current envelope that defines afirst series of pulses occurring at a 4 Hz frequency, when delivered tothe patient, may tend to evoke a metabolic cleansing response. It hasalso been discovered that the definition by the stimulation currentenvelope of a second series of pulses occurring at a 40 Hz frequency,when delivered to the patient, may tend to promote a neuronalregenerative response. Thus, it is contemplated that a stimulationcurrent having a stimulation current envelope that defines both a 4 Hzfirst series of pulses and a 40 Hz second series of pulses may bedelivered to a patient in order to achieve both of these results.Further, it is contemplated that by varying the frequency least one ofthe two series of pulses over time during the administration of atreatment regimen, a synergistic beneficial effect may be realized as aresult of the different neural entrainment outcomes resulting from theparticular choices used. For example, in one particular embodiment, thestimulation current may have a stimulation current envelope defining afirst series of pulses occurring at a constant 40 Hz frequency for theentire duration of the treatment, with the stimulation current envelopealso defining a second series of pulses occurring at a variablefrequency, the variable frequency being 4 Hz for a first portion of thetreatment, 40 Hz for a second portion of the treatment, and 77.5 Hz fora third portion of the treatment. It is further contemplated that for atreatment with a duration of an hour, each of the first, second, andthird portions of treatment may be roughly equal, i.e. be 20 minutes inlength. As such, the transcranial electrostimulation device may beconfigured to output a stimulation current according to theseparameters. It may also be seen that via the delivery of a stimulationcurrent having different frequency and amplitude patternscharacteristics of its combined stimulation current envelope, multipledifferent neural regions may be configured to be stimulated in variousways across a single course of treatment, according to the effectsdesired to be achieved via such stimulation treatment regimens.

Turning now to FIG. 4, an example of a resultant rectified charge thatis entrained at the neurons within the occipital region of a patient'sbrain as a result of delivery of an exemplary stimulation current to theoccipital region of the patient's brain is shown overlaid atop thatexemplary stimulation current. It may be seen that this resultantrectified charge may occur as a consequence of transcranial applicationof the illustrated stimulation current to occipital region of apatient's brain, which causes this rectified charge to accrue at theneurons. This rectified charge accrual results in polarization of theelectrical charge on the outside of the neural membrane, in accordancewith the frequency of the first series of pulses defined by the envelopeof the stimulation current. As long as the magnitude and pulse width ofthe pulses defined by the stimulation current envelope are sufficient tocause sufficient accrual of electrical charge at a neuron to elevate theresting potential of the neuron to the threshold of excitation, anaction potential of the neuron will be triggered. As may be seen, ahigher magnitude pulse of a lesser pulse width may be sufficient tocause enough charge to accrue, or a lower magnitude pule of a greaterpulse width may be sufficient, so long as the sufficient voltage isachieved at the membrane of the neuron as a result of delivery of thestimulation current. Further, it may be seen that so long as thefrequency of the series of pulses are not too high (i.e. longer than theneuronal refractory period) each pulse will separate trigger anotheraction potential within the neuron in order to cause natural entrainmentto the frequency of the first series pulses. It may further be seen,however, that configurations of the different parameters of stimulationcurrents may result in some pulses being received at some neurons priorto the recovery of the neuronal refractory period resulting fromtriggering of the action potential by an earlier pulse. Such schemes maybe utilized in order to, for example, target entrainment of certaintypes or localities of neurons according to a first frequency, and totarget entrainment of another type or locality of neurons according to asecond frequency.

Turning now to FIG. 5, a flowchart showing certain steps of anembodiment of a method for treating a patient for Alzheimer's Dementiavia the dynamic delivering a charge balanced alternating currentelectrical signal to the occipital region of a patient's brain is shown.In particular, it is contemplated that a TCES system may first digitallysynthesize one or more high frequency rectangular AC carrier waveforms,which may or may not be similar to the waveform illustrated in FIG. 1.The TCES system may then amplitude modulate the high frequency carrierwaveform, as described in detail above, according to the particularparameters ultimately desired in the stimulation current, ultimatelyproducing a stimulation current, which will then be conveyed to thepatient. It is further contemplated that in certain embodiments, ameasurement of electrode contact impedance may be taken at the patientat the point of delivery of the stimulation current via one or morereference electrodes. In these embodiments, the stimulation current maythen be controlled (such as via alternation of the parameters of thehigh frequency carrier waveform, or by alteration of the various factorsof the amplitude modulation) in order to better optimize the performanceof the stimulation current, to confirm electrode contact quality, and toprevent any current imbalances that may result in unequal stimulation orinadvertent generation of DC components that may result in discomfort tothe patient.

Turning now to FIG. 6, a block diagram of an exemplary TranscranialAlternating Current Dynamic Frequency Stimulation (TACS) system isillustrated. As may be seen, one exemplary embodiment of a TACS systemmay comprise a device chassis containing an AC/DC power supply, astimulation circuitry printed circuit board (PCB), a front panel PCB,and a battery pack, configured for use with an external mains powersource that feeds into the AC/DC power supply. Also included is apatient cable for conveying the stimulation current to the patient maybe attached to the stimulation circuitry PCB, with the patient cablehaving a right active electrode, a left active electrode, and areference electrode. While this specific block diagram shows oneexemplary version of a TACS system, it is certainly not the onlyconfiguration in which the systems and methods herein described may beachieved, and indeed, these descriptions of the actual physicalarchitecture of a TACS system are to be understood as being purely forexemplary purposes in order to enable the reader to more fullyunderstand the nature of the herein described systems and methods, andare not to be interpreted as representing or imposing any limitations ofthe subject matter described herein. For example, but withoutlimitation, it may not be necessary for some or all components to becontained within a physical device chassis, or for many of thesecomponents to be present in the exact form described or at all.

The stimulation circuitry PCB may be for controlling the functionalityof the TACS related to the generation and control of the stimulationcurrent, including the synthesis of a high frequency carrier waveform.In this respect, it is to be understood as including as subsidiarycomponents (which may be hardware or software components, orcombinations thereof) both the waveform generator and the stimulationcurrent generator. The stimulation circuitry PCB will be more fullydescribed in relation to the foregoing discussion of FIG. 7.

The front panel PCB may be for supporting the user interface for theTACS system, and may include, for example, means for user input and fordisplay of information to the user. The front panel PCB will be morefully described in relation to the foregoing discussion of FIG. 8.

The patient cable may be for conveying the stimulation current producedat the TACS to the patient. The patient cable may include or beconnected to two or more active electrodes for delivering thestimulation current to the patient, and may further include or beconnected to one or more reference electrodes for determiningstimulation output voltage and returning measurements which will be usedto determine electrode impedance. The active electrodes may comprise apliable substrate with an electrically conductive adhesive. In anexemplary embodiment configured for frontal cortical stimulations, theactive electrodes may be applied to the left and right mastoid region ofthe patient, with the reference electrode applied to the patient'sforehead. However, it may be seen that in other configuration which maybe optimized for other types of stimulation, the location, positioning,quantity, etc. of the active electrodes and the reference electrode(s)may be different.

The power supply, which in the exemplary embodiment may be optional andwhich may be a medical grade AC/DC power supply, may be any power supplyor other which may be used to receive mains power and to permit thatmains power to be conveyed the remainder of the system and utilized toultimately produce a stimulation current. Likewise, the battery pack,which again may be an optional component, and which in the exemplaryembodiment is a Ni-MH battery pack that also includes a batterymanagement system, may serve to provide uninterrupted power during mainspower failure, and which may serve to prevent artifact generation(spikes, jitters, etc.) that may occur during failure or intermittentlosses or reduction in mains power delivery, as such artifacts may beincluded within the stimulation current which may result in inadvertentrectification of the stimulation by the skin and production of a DCcurrent component, leading to patient discomfort. However, it may beseen that the presence or absence of these components are not ofcritical importance to the systems or methods herein disclosed, andthat, such systems or methods may be performed without a battery pack ora power supply, so long as the mains power or other source of currentused to produce the stimulation current is sufficient to enableperformance of the herein discussed methods.

Turning now to FIG. 7, a block diagram showing, in greater detail,certain hardware and/or software components of a stimulation circuitryPCB according to one embodiment of a transcranial electrostimulationsystem for treating a patient for Alzheimer's Dementia. As may be seen,the stimulation circuitry PCB may, in the exemplary embodiment shown,include a stimulation circuit microcontroller comprising a centralprocessing unit (CPU), a waveform generator module, a waveformmodulation module, and an analog to digital converter (ADC) module, withthe stimulation circuitry PBC also including a digital to current sourceconverter module, a voltage and current sense module, a digitalpotentiometer (pot), a Ni-MH battery management module, a powerconditioning module, and inputs/outputs to the front panel PCB and tothe patient cable. While this specific block diagram shows one exemplaryversion of the stimulation circuitry of a TACS system, it is certainlynot the only configuration in which the systems and methods hereindescribed may be achieved, and indeed, these descriptions of thephysical and/or digital architecture of the stimulation circuitry of aTACS system are to be understood as being purely for exemplary purposesin order to enable the reader to more fully understand the nature of theherein described systems and methods, and are not to be interpreted asrepresenting or imposing any limitations of the subject matter describedherein. It is also to be understood that the respective modulesdescribed herein may be implemented in hardware, in software, or incombinations of hardware and software, including as subsidiarycomponents of one another or integrated together.

The CPU may provide software control of all hardware functions in theTACS system. The CPU may also receive inputs from the ADC module andperform calculations based upon those inputs in order to control thefunctionality of the TACS system and its subordinate components in realtime.

The carrier waveform generator module may be controlled by the CPU andmay generate a carrier waveform according to the specific parametersdesired, which may include a duty cycle and current amplitude ratio. Thecarrier waveform may then be then amplitude modulated with a carrierwaveform via a digital potentiometer controlled by a waveform modulationmodel (also potentially controlled by the CPU) to perform the hereindescribed steps in order to produce a digital representation of theherein described stimulation current. According to a preferredembodiment, the carrier waveform and thus the resulting stimulationcurrent has a frequency of about 100 KHz.

Following amplitude modulation of the carrier waveform, a digital tocurrent source converter, i.e. the stimulation current generator, may beused to ultimately generate, from a digital representation of theamplitude modulated carrier waveform, the actual stimulation current forsubsequent delivery to the patient. According to a preferred embodiment,the stimulation current is about 15 mA. However, it may be seen that thestimulation current flow may also be at different rates.

The ADC module may be configured to receive analog information from avoltage and current sense module and to convert that analog informationto digital information for use by the CPU in order to permit real-timeadjustment of the stimulation current. Such analog information may be,according to certain contemplated embodiments, information received froman active electrode or a reference electrode, which may concern qualityof electrode contact, electrical impedance, etc. Such information may beused to provide feedback to the CPU and to permit dynamic adjustments tobe made in real time to the stimulation current, such as via adjustmentof the underlying waveform, the modulation signal(s), or directly at thestimulation current itself.

In the exemplary embodiment, a power conditioning module may also beincluded within or in relation to the stimulation circuitry PCB forregulating the power supply to voltage supply rails for the operation ofthe microcontroller and the stimulation output circuitry.

Turning now to FIG. 8, a block diagram is illustrated that shows certainhardware and/or software components of a front panel of an exemplaryembodiment of a transcranial electrostimulation system for treating apatient for Alzheimer's Dementia. In this exemplary embodiment, thefront panel may be seen to include a membrane array switch and a LEDsegment display array. The membrane array switch may be utilized by theuser of the TECS system in order to manually input adjustments to theparameters of the stimulation current, such as output level, treatmenttime, or treatment controls. The LED segment display array may be viewedby the user to visually confirm these parameters and the overall statusof the device. It is to be understood that a this description of a frontpanel is purely illustrative in nature and is specific to one exemplaryembodiment of a TECS system, and that the presence, absence, or specificconfiguration of any front panel, or any panel located anywhere on anysuch device, or the controls or displays contained therein, are purelyillustrative of merely one particular embodiment, and these descriptionsare certainly not meant to impose any limitations on the inventiveaspects of the herein described systems and methods.

Turning now to FIG. 9, an exemplary image of a front panel userinterface of an embodiment of a transcranial electrostimulation systemfor treating a patient for Alzheimer's Dementia is shown. It may be seenthat the front panel user interface may, according to the particularembodiment illustrated, include controls from adjusting an output, whichmay be a current level setpoint (i.e. in milliamperes) or even analphanumeric signifier that relates to a treatment type, such as theoutput of a stimulation current according to one of the manyaforementioned variations in frequency or multiple frequencies, or anentire set of predefined treatment parameters encompassed within atreatment modality. A treatment time may also be adjusted, as well as amanual start/stop button for beginning or ending the treatment. Thefront panel user interface may also contain, without limitation, one ormore status LEDs for indicating a status condition, such as a batterystatus (i.e. fully charged, low charge, no charge remaining, etc.), acheck electrode status (i.e. no or poor contact of one or moreelectrodes), or a general fault status which may indicate otherconditions not encompassed by other status indicators. However, it is tobe understood that a this description of a front panel user interface ispurely illustrative in nature and is specific to one exemplaryembodiment of a TECS system, and that the presence, absence, or specificconfiguration of any front panel user interface, or the controls ordisplays contained thereon or therein, are purely illustrative of merelyone particular embodiment, and these descriptions are certainly notmeant to impose any limitations on the inventive aspects of the hereindescribed systems and methods.

The above description is given by way of example, and not limitation.Given the above disclosure, one skilled in the art could devisevariations that are within the scope and spirit of the inventiondisclosed herein. Further, the various features of the embodimentsdisclosed herein can be used alone, or in varying combinations with eachother and are not intended to be limited to the specific combinationdescribed herein. Thus, the scope of the claims is not to be limited bythe exemplary embodiments.

What is claimed is:
 1. A transcranial electrostimulation system fortreating a patient for Alzheimer's Dementia, the transcranialelectrostimulation system comprising: a carrier waveform generator; astimulation current generator, a stimulation current being generatedfrom a carrier waveform output from the waveform generator, the carrierwaveform being an alternating current having a duty cycle ratio and acurrent amplitude ratio, the duty cycle ratio and the current amplituderatio being selected such that each respective pair of integrations ofthe current amplitude between successive time instances at which thecarrier waveform alternates polarity is substantially equivalent; and apatient cable connectable to the stimulation current generator and tothe patient, the stimulation current being conveyed to the patient viathe patient cable.
 2. The transcranial electrostimulation system ofclaim 1, wherein the stimulation current is generated via amplitudemodulation of the carrier waveform, the extremes of the stimulationcurrent defining a stimulation current envelope.
 3. The transcranialelectrostimulation system of claim 2, wherein the stimulation current isgenerated via amplitude modulating the carrier waveform such that thestimulation current envelope defines a first series of pulses occurringat a first frequency.
 4. The transcranial electrostimulation system ofclaim 3, wherein the first series of pulses occur at a frequency ofabout 40 Hz.
 5. The transcranial electrostimulation system of claim 3,wherein the stimulation current envelope further defines a second seriesof pulses occurring at a second frequency.
 6. The transcranialelectrostimulation system of claim 4, wherein the second series ofpulses occur at a frequency selected from: about 4 Hz, about 40 Hz,about 77.5 Hz.
 7. The transcranial electrostimulation system of claim 5,wherein the stimulation current is conveyed to the patient for atreatment duration, wherein the first series of pulses occurs at afrequency about 40 Hz for the entire treatment duration, and wherein thesecond series of pulses occur at a frequency of about 4 Hz for a firstportion of the treatment duration, about 40 Hz for a second portion ofthe treatment duration, and about 77.5 Hz for a third portion of thetreatment duration.
 8. The transcranial electrostimulation system ofclaim 7, wherein the treatment duration is about an hour, and whereineach of the first portion of the treatment duration, the second portionof the treatment duration, and the third portion of the treatmentduration are about 20 minutes.
 9. The transcranial electrostimulationsystem of claim 2, wherein the stimulation current is generated viaamplitude modulating the carrier waveform such that the stimulationcurrent envelope defines a plurality of series of pulses, eachrespective one of the plurality of series of pulses occurring at arespective frequency.
 10. The transcranial electrostimulation system ofclaim 9, wherein each of the plurality of series of pulses occurs at afrequency selected from one or more of: about 4 Hz, about 40 Hz, about77.5 Hz.
 11. The transcranial electrostimulation system of claim 1,wherein the carrier waveform has a frequency of about 100 KHz.
 12. Thetranscranial electrostimulation system of claim 1, wherein the carrierwaveform is a rectangular wave.
 13. The transcranial electrostimulationsystem of claim 1, further comprising one or more reference electrodes,the stimulation current being measured at the patient by the one or morereference electrodes and an electrode contact impedance being determinedtherefrom, and a controller in communication with the one or morereference electrodes, the controller adjusting, based upon thedetermined electrode contact impedance, one or more parameters of: thecarrier waveform output from the waveform generator, the stimulationcurrent output from the stimulation current generator, or combinationsthereof.
 14. A method for treating a patient for Alzheimer's Dementia,the method comprising: (a) generating a stimulation current via thesteps of: generating a carrier waveform, the carrier waveform being analternating current having a duty cycle ratio and a current amplituderatio, the duty cycle ratio and the current amplitude ratio beingselected such that each respective integration of the current amplitudebetween successive time instances at which the carrier waveformalternates polarity is substantially equivalent; and generating astimulation current from the carrier waveform via amplitude modulatingthe carrier waveform, the extremes of the stimulation current defining astimulation current envelope, the stimulation current envelope defininga first series of pulses occurring at a first frequency; and (b)Applying the stimulation current to the occipital region of the brain ofthe patient.
 15. The method of claim 14, wherein the first series ofpulses occur at a frequency of about 40 Hz.
 16. The method of claim 14,wherein the stimulation current is generated via amplitude modulatingthe carrier waveform such that the stimulation current envelope currentfurther defines a second series of pulses occurring at a secondfrequency.
 17. The method of claim 16, wherein the second series ofpulses occur at a frequency selected from: about 4 Hz, about 40 Hz,about 77.5 Hz.
 18. The method of claim 16, wherein the method comprisesapplying the stimulation current to the occipital region of the brain ofa to a patient for a treatment duration, wherein the first series ofpulses occurs at a frequency of about 40 Hz for the entire treatmentduration, and wherein the second series of pulses occurs at frequency ofabout 4 Hz for a first portion of the treatment duration, a frequency ofabout 40 Hz for a second portion of the treatment duration, and afrequency of about 77.5 Hz for a third portion of the treatmentduration.
 19. The method of claim 18, wherein the treatment duration isabout an hour, and wherein each of the first portion of the treatmentduration, the second portion of the treatment duration, and their thirdportion of the treatment duration are about 20 minutes.
 20. The methodof claim 14, wherein in step (a), the stimulation current is generatedvia amplitude modulating the carrier waveform such that the stimulationcurrent envelope defines a plurality of series of pulses, eachrespective one of the plurality of series of pulses occurring at arespective frequency
 21. The method of claim 20, wherein each of theplurality of stimulation current envelopes has a frequency selected fromone or more of: about 4 Hz, about 40 Hz, about 77.5 Hz.
 22. The methodof claim 14, wherein the carrier waveform has a frequency of about 100KHz.
 23. The method of claim 14, wherein the carrier waveform is arectangular wave.
 24. The method of claim 14, further comprising thesteps of measuring the stimulation current at the patient anddetermining an electrode contact impedance therefrom, and based upon thedetermined electrode contact impedance, adjusting one or more parametersof one or more of: the carrier waveform output from the waveformgenerator, the stimulation current output from the stimulation currentgenerator, or combinations thereof.
 25. A method of generating astimulation current, the method comprising: generating a carrierwaveform, the carrier waveform being a rectangular alternating currenthaving a first duty cycle ratio and a first current amplitude ratio, thefirst duty cycle ratio and the first current amplitude ratio beingselected such that each respective integration of the current amplitudebetween successive time instances at which the waveform alternatespolarity is substantially equivalent; and amplitude modulating thecarrier waveform to derive a stimulation current, the extremes of thestimulation current defining a stimulation current envelope, thestimulation current envelope defining a first series of pulses occurringat a first frequency.